PmrA-PmrB-regulated Genes Necessary for 4-aminoarabinose Lipid A Modification and Polymyxin Resistance

Mol Microbiol. 1998 Mar;27(6):1171-82. doi: 10.1046/j.1365-2958.1998.00757.x.

Abstract

Antimicrobial peptides are distributed throughout the animal kingdom and are a key component of innate immunity. Salmonella typhimurium regulates mechanisms of resistance to cationic antimicrobial peptides through the two-component systems PhoP-PhoQ and PmrA-PmrB. Polymyxin resistance is encoded by the PmrA-PmrB regulon, whose products modify the lipopolysaccharide (LPS) core and lipid A regions with ethanolamine and add aminoarabinose to the 4' phosphate of lipid A. Two PmrA-PmrB-regulated S. typhimurium loci (pmrE and pmrF) have been identified that are necessary for resistance to polymyxin and for the addition of aminoarabinose to lipid A. One locus, pmrE, contains a single gene previously identified as pagA (or ugd) that is predicted to encode a UDP-glucose dehydrogenase. The second locus, pmrF, is the second gene of a putative operon predicted to encode seven proteins, some with similarity to glycosyltransferases and other complex carbohydrate biosynthetic enzymes. Genes immediately flanking this putative operon are also regulated by PmrA-PmrB and/or have been associated with S. typhimurium polymyxin resistance. This work represents the first identification of non-regulatory genes necessary for modification of lipid A and subsequent antimicrobial peptide resistance, and provides support for the hypothesis that lipid A aminoarabinose modification promotes resistance to cationic antimicrobial peptides.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Anti-Bacterial Agents / pharmacology
  • Arabinose / analogs & derivatives*
  • Arabinose / metabolism
  • Bacterial Proteins / genetics*
  • Bacterial Proteins / physiology
  • Cloning, Molecular
  • Drug Resistance, Microbial / genetics*
  • Genes, Bacterial / genetics
  • Genes, Reporter / genetics
  • Lipid A / chemistry*
  • Molecular Sequence Data
  • Mutagenesis / genetics
  • Operon / genetics
  • Polymyxins / pharmacology*
  • Salmonella typhimurium / genetics*
  • Sequence Analysis, DNA
  • Uridine Diphosphate Glucose Dehydrogenase / physiology

Substances

  • Anti-Bacterial Agents
  • Bacterial Proteins
  • Lipid A
  • PhoQ protein, Bacteria
  • Polymyxins
  • aminoarabinose
  • pmrA protein, Bacteria
  • PhoP protein, Bacteria
  • Arabinose
  • Uridine Diphosphate Glucose Dehydrogenase

Associated data

  • GENBANK/AF036677